Wednesday 09 December 2015
Researchers at the Peter MacCallum Cancer Centre are pioneering the development of a new combination drug therapy to treat advanced blood cancers which has doubled survival times in pre-clinical laboratory models.
Their study, published overnight in Cancer Discovery, builds on a world-first clinical trial already underway at Peter Mac which uses the drug CX-5461 to treat patients with incurable blood cancers such as myeloma, lymphoma and leukaemia.
The trial has shown promising results to date, however the research team has found that CX-5461 could be even more effective when used in combination with another drug, Everolimus, which is already used to treat other cancers.
According to Professor Rick Pearson, Head of Peter Mac’s Cancer Signaling Laboratory, the research findings significantly enhance understanding of pre-emptive strategies to kill off cancer cells before they have the chance to become resistant to therapy.
“CX-5461 targets a particular process that is required for cancer cell survival. Our experiments show that adding Everolimous synergistically strengthens this attack, more rapidly and more effectively eradicating the killer disease.
“We know that all cells rely on ribosomes which act like a factory producing the proteins essential for their growth and survival,” according to Professor Pearson.
“Peter Mac researchers have previously shown that certain blood cancers are far more reliant on these proteins than normal cells, and that eliminating the protein production capability of ribosomes leads to the rapid death of cancer cells, while normal cells stay viable.
“As a result of this research breakthrough, fifteen patients are currently involved in a phase 1 clinical trial of CX-5461 – a compound that our research team is developing with pharmaceutical company Senhwa.
“This novel therapy works to inhibit the ribosomes’ protein production capability, effectively starving the cancer cells of a key ingredient they need to survive and proliferate.
“By adding Everolimus to this treatment, we have shown the potential for even more powerful results. A further study in collaboration with scientists at Monash University shows striking effects in the targeting of late stage prostate cancer through a similar strategy indicating that this approach may be generally applicable for a range of cancer types.”
Associate Professor Simon Harrison, Consultant Haematologist at Peter Mac and Principal Investigator on the CX-5461 first-in-human trial, says this new research provides further confidence that researchers are on the right track.
“The prevalence and poor prognosis for people with advanced blood cancers demands the ongoing and intricate study of abnormal cell behaviour, which has been an indicator of cancer for over 100 years. To date 15 patients have been treated on the first-in-human clinical study with a number of patients experiencing prolonged benefit.
“With this new knowledge we can now work closely with pharmaceutical companies to potentially fast track the testing of this combination approach for the benefit of patients.”
More than 12,000 Australians are diagnosed with blood cancer annually (approximately 10% of all cancers) and around 4,000 Australians will lose their lives to the disease each year.
This research is supported by the National Health and Medical Research Council; Cancer Council Victoria; the Leukemia Foundation; Prostate Cancer Foundation of Australia; Cancer Australia; Victorian Cancer Agency, Australian Cancer Research Foundation and Peter MacCallum Cancer Foundation. Collaborators include the John Curtain School of Medical Research at the Australian National University and Monash University.